Polycyclic chlorinated amines

ABSTRACT

A compound having one of the structural formulae: ##STR1## AND HYDROGENATED, CHLORINATED AND BROMINATED DERIVATIVES THEREOF; ##STR2## WHEREIN R is H or lower alkyl; ##STR3## WHEREIN X is Cl or Br and n is an integer from 0 to 6; ##STR4## WHEREIN X is Cl or Br and m is an integer from 0 to 8; ##STR5## AND HYDROGENATED, CHLORINATED AND BROMINATED DERIVATIVES THEREOF; AND, ##STR6## USEFUL AS INSECTICIDES.

RELATIONSHIP TO OTHER APPLICATIONS

This is a division of application Ser. No. 778,114, filed Mar. 16, 1977,now U.S. Pat. No. 4,115,391, which is a divisional of Ser. No. 672,322,filed Mar. 31, 1976, now U.S. Pat. No. 4,081,448, which is in turn acontinuation-in-part application of application Ser. No. 445,576, filedMar. 25, 1974 now abandoned.

BACKGROUND OF THE INVENTION

A well-known class of insecticides includes the polychlorinated cyclichydrocarbons with endomethylenebridged structures. These compounds areprepared by the well-known Diels-Alder [4+2] cyclo-addition reaction.

The tradenames of various of these insecticides are: Chlordane,Heptachlor, Heptachlor expoxide, Betadihydroheptachlor, Telodrin,Aldrin, Dieldrin, Endrin, Endosulfan (Thiodan), Aldodan, Mirex andNonachlor.

These insecticides are conventionally used for the control ofcockroaches, ants, termites and other household pets, soil insects and avariety of vegetable and field crop pests. They are good contactinsecticides whose symptoms of poisoning include disturbance of theganglia of the central nervous system upon absorption by the insect.

SUMMARY OF THE INVENTION

The present invention relates to a novel class of compounds possessingan activity similar to the polychlorinated cyclic hydrocarbons. Thecompounds of the invention are, in essence, the bridgehead nitrogenanalogs of the above-mentioned commercial insecticides. They possess,generally, the same or better insecticidal properties, however, areadvantageous in that they are more readily degraded after performingtheir function thereby lessening the deleterious impact on theenvironment.

The chlorinated polycyclic amines of the present invention are preparedby reacting pentachloro-α-pyrrolenine with norbornadiene,cyclopentadiene or other appropriate olefin in a Diels-Alder typecyclo-addition, followed by, in some instances- further treatment toyield a desired derivative.

DETAILED DESCRIPTION OF THE INVENTION

The compounds of the invention have the following structural formulae:##STR7## and hydrogenated, chlorinated and brominated derivativesthereof; ##STR8## wherein R is H or lower alkyl; ##STR9## wherein X isCl or Br and n is an integer from 0 to 6; ##STR10## wherein X is Cl orBr and m is an integer from 0 to 8; ##STR11## and hydrogenated,chlorinated and brominated derivatives thereof; and, ##STR12##

The reactions involved are exemplified by the following reactionschemes: ##STR13##

The chlorinated polycyclic amines of the invention are highly activeinsecticides. They are superior to the above-described chlorinatedinsecticides in that they are readily degradable whereas the chlorinatedcommercial insecticides are not. The latter have been found to bedisadvantageous due to the accumulation of their residues in theenvironment posing a threat to the general health. As a consequencetheir use has been stringently regulated on both the Federal and statelevels. Moreover, the pest colonies have developed widespread resistanceto the above-described chlorinated hydrocarbon insecticides.

The polycyclic amines of the present invention lend themselves torelatively easy hydrolysis at the bridgehead nitrogen due to thepresence of the N - CCl₂ moiety to an amino acid which may bebiodegraded further. This degradation pathway is unavailable to theabove-described commercial insecticides and is highly advantageous inthat it solves the notorious residue problem associated therewith.

The presence of the bridgehead amino moiety also enhances thepharmacological effects of the insecticide on the nervous system of theinsects. This enhancement of insecticidal efficiency reduces the problemof pest resistance considerably.

EXAMPLE 1

A mixture of 1 g (4.2 mmol) of pentachloro-α-pyrrolenine (Mazzara,Gazzetta Chemica Italiana, 32 II, 30, 1902) and 0.425 ml (4.2 mmol) ofnorbornadiene was placed in a sealed tube and heated at 80° C. for 4days. The reaction product was dissolved in 50% acetone-methanol andfiltered through charcoal. The filtrate was evaporated andrecrystallized five times from acetone-methanol yielding 1.10 g (80%) of1-aza-2,3,4,10,10-pentachloro-1,4,4a,5,8a-hexahydro-1,4:5,8-dimethanonaphthalene,m.p., 97°-99° C. Anal. Calcd. for C₁₁ H₈ NCl₅ :C,39.81; H,2.41; N,4.22.Found: C, 39.99; H,2.22; N,4.06.

The compound may be represented by the formula: ##STR14##

EXAMPLE 2

A mixture of 2 g (8.4 mmol) of pentachloro-α-pyrrolenine and 0.556 g(8.4 mmol) of cyclopentadiene was allowed to stand at room temperatureovernight. The reaction mixture was dissolved in 50% aqueous ethanol andcooled. The precipitate was recovered and sublimed at 55° C., 0.1 mm toyield 1.9 g (74%) of product, m.p. 173°-174° C.

Anal. Calcd. for C₉ H₆ NCl₅ ; C, 35.35; H, 1.96; N, 4.58. Found: C,35.36; H, 1.94; N, 4.46.

The compound may be represented by the formula: ##STR15##

EXAMPLE 3

A mixture of 3.0 g (9.05 mmol) of the compound of Example 1 and 1.725 g(10 mmol) of m-chloroperbenzoic acid in 20 ml of chloroform was stirredat room temperature for 14 days. The reaction mixture was extractedsuccessively with 3×3 ml of 5% aqueous sodium bisulfite solution and 3×3ml of 5% aqueous solution bicarbonate solution. The organic layer wasdried, evaporated, and the residue recrystallized three times from etherand sublimed at 60°/0.1 mm, yielding 2.3 g of1-aza-2,3,4,10,10-pentachloro-6,7-epoxy-1,4,4a,5,6,7,8,8a-octahydro-1,4-endo-exo-5,8-dimethanonaphthalene.Anal. Calcd. for C₁₁ H₈ NOCl₅ : C, 37.98; H, 2:30; N, 4.02. Found: C,38.24; H, 2.21; N, 3.82.

The compound of Example 3 may be represented by the formula: ##STR16##

EXAMPLE 4

A mixture of 5.0 g (16.37 mmol) of the compound of Example 2 and 3.02 g(17.5 mmol) of m-chloroperbenzoic acid in 25 ml of chloroform wasstirred at room temperature for 14 days. The reaction mixture wasextracted successively with 3×3 ml of 5% aqueous sodium bisulfitesolution and 3×3 ml of 5% aqueous sodium bicarbonate solution. Theorganic layer was dried, evaporated, and the residue recrystallizedthree times from ether, yielding 3.40 g of product.

Anal. Calcd. for C₉ H₆ NOCl₅ : C, 33.59; H, 1.86; N, 4.35. Found: C,33.79; H, 1.80; N, 3.99.

The compound of Example 4 may be represented by the formula: ##STR17##

EXAMPLE 5

A mixture of 175 mg (0.574 mmol) of the compound of Example 2 and 92 mg(0.574 mmol) of bromine in 15 ml of methylene chloride was stirred atroom temperature for 4 days. The solution was evaporated and the residuesublimed to yield 230 mg of product.

The compound may be represented by the formula: ##STR18##

EXAMPLE 6

The compounds of Examples 1 and 2 were evaluated as mosquito larvicidesand body louse toxicants according to the following methods.

Body Louse Toxicant

Compounds are screened as body louse (pediculus humanus humanus L.)toxicants by exposing young adult body lice on treated patches of woolencloth,3.8 cm in diameter. Duplicate patches are impaled on pinboards,and 0.7 ml of 1% solutions of the compounds in acetone or anothervolatile solvent is applied to them by pipette. After the patches aredried, 10 female lice are exposed to them in 50-ml glass beakers for 24hours. Patches on which all lice are dead or knocked down are retestedat intervals of 2 to 7 days until one or more lice remain unaffected.After 31 days the tests are terminated, even if the patches are stilleffective. DDT and malathion standards and an untreated patch areincluded for comparison. The standards are usually effective for morethan 31 days under these conditions.

Mosquito Larvicides

Compounds are screened as mosquito larvicides by exposing early4th-instar larvae of Anopheles quadrimaculatus Say to solutions orsuspensions of the compounds in water (duplicate tests). The compoundsare dissolved in acetone and added to water; water-soluble compoundsremain in solution and the others become finely divided suspensions.Mosquito larvae are added to the treated water and mortality isdetermined after 24 hours of exposure. If 95% to 100% mortality occursat the initial concentration of 10 parts per million, additional testsare made to determine the minimum effective concentration. Under theseconditions, the LC 90 of the standard larvicide Abate®, is 0.005 ppm.

As a residual louse toxicant, the compound of Example 1 remained 100%effective for >31 days whereas the compound of Example 2 was 100%effective for 17 days. In speed of action, the compound of Example 1required 1 hour to produce 100% knockdown of lice exposed to the freshtreatment. The compound of Example 2 required >3 hours but <24 hours toproduce 100% knockdown.

As mosquito larvicides, the compound of Example 1 produced mortalitiesof 100% and 96% at the 10 and 1 ppm concentrations, respectively. Thecompound was 20% effective at 0.1 ppm concentration.

EXAMPLE 7

The compounds of Examples 1 and 2 were compared with their commercialanalogs, Aldrin and Chlordene as insecticides. The following testparameters were employed:

Host: cockroach ca. 1 g size. Vehicle: 95% ethanol. Mode of application:dropping ca. 50 μl of solution onto roach back using a microsyringe.Blank: 95% ethanol.

The results are set forth below:

    ______________________________________                                                        Observation                                                             Dosage      Onset of nervous                                                                           Death                                      Compound  (mol/g of host)                                                                           disorder after, hr.                                                                        after, hr.                                 ______________________________________                                        Aldrin    3 × 10.sup.-6                                                                       3            36                                         Cmpd. of Ex. 1                                                                          3 × 10.sup.-6                                                                       2            24                                         Chlordene 7 × 10.sup.-6                                                                        24          48                                         Cmpd. of Ex. 2                                                                          7 × 10.sup.-6                                                                       1            36                                         Blank     75 μl    no effect    no effect                                  ______________________________________                                    

The epoxidated compounds of Examples 3 and 4 may be prepared by reactingthe starting material with any conventionally employed per-acid, e.g.,peracetic acid, perbenzoic acid, per-chlorobenzoic acid,per-trifluorobenzoic acid, etc.

I claim:
 1. A compound having a structural formula selected from thegroup consisting of: ##STR19## wherein R is H₂,lower alkyl; ##STR20##wherein X is Cl or Br and N is an integer from 0 to 6; ##STR21## whereinX is Cl or Br and m is an integer from 0 to 8.